Infections with Clostridium difficile can lead to severe, even life-threatening diarrhoea. The symptoms are caused by two toxins synthesized by C. difficile, TcdA and TcdB. The toxins can enter the cells lining the colon, where they are activated by cytosolic inositol hexakisphosphate (IP6) and exert their toxic function. One suggested therapeutic intervention is to activate the toxins in the extracellular space of the colon lumen. The activated toxins are no longer able to enter the colon cells, and within the colon lumen they cannot exert their toxic function. Thus, activation of the toxins within the colon lumen renders the toxins harmless for the affected patient.
IP6 cannot be used for therapeutic intervention, because it precipitates due to the high calcium concentration in the colon lumen.
WO2013045107A1 shows PEG-modified inositol phosphate compounds and mixed inositol phosphate-sulfate compounds and their use in activation of C. difficile toxin activation. The activity of the compounds shown therein is promising, however improvements upon the results related therein would be of advantage. Thus, the problem underlying the present invention is to provide activators of C. difficile toxin that exhibit stronger activity at high calcium concentration.
This problem is solved by the subject matter of the independent claims.